Combination of the Topical Photodynamic Therapy of Chloroaluminum Phthalocyanine Liposomes with Fexinidazole Oral Self-Emulsifying System as a New Strategy for Cutaneous Leishmaniasis Treatment.

Cutaneous leishmaniasis (CL) is a neglected tropical disease. The treatment is restricted to drugs, such as meglumine antimoniate and amphotericin B, that exhibit toxic effects, high cost, long-term treatment, and limited efficacy. The development of new alternative therapies, including the identification of effective drugs for the topical and oral treatment of CL, is of great interest. In this sense, a combination of topical photodynamic therapy (PDT) with chloroaluminum phthalocyanine liposomes (Lip-ClAlPc) and the oral administration of a self-emulsifying drug delivery system containing fexinidazole (SEDDS-FEX) emerges as a new strategy. The aim of the present study was to prepare, characterize, and evaluate the efficacy of combined therapy with Lip-ClAlPc and SEDDS-FEX in the experimental treatment of Leishmania (Leishmania) major. Lip-ClAlPc and SEDDS-FEX were prepared, and the antileishmanial efficacy study was conducted with the following groups: 1. Lip-ClAlPc (0.05 mL); 2. SEDDS-FEX (50 mg/kg/day); 3. Lip-ClAlPc (0.05 mL)+SEDDS-FEX (50 mg/kg/day) combination; 4. FEX suspension (50 mg/kg/day); and 5. control (untreated). BALB/c mice received 10 sessions of topical Lip-ClAlPc on alternate days and 20 consecutive days of SEDDS-FEX or FEX oral suspension. Therapeutical efficacy was evaluated via the parasite burden (limiting-dilution assay), lesion size (mm), healing of the lesion, and histological analyses. Lip-ClAlPc and SEDDS-FEX presented physicochemical characteristics that are compatible with the administration routes used in the treatments. Lip-ClAlPc+SEDDS-FEX led to a significant reduction in the parasitic burden in the lesion and spleen when compared to the control group (p < 0.05) and the complete healing of the lesion in 43% of animals. The Lip-ClAlPc+SEDDS-FEX combination may be promising for the treatment of CL caused by L. major.

Integrated Ca, Mg, Cu, and Zn supply upregulates leaf anatomy and metabolic adjustments in Eucalyptus seedlings.

Adaptive responses to abiotic stresses such as soil acidity in Eucalyptus-the most widely planted broad-leaf forest genus globally-are poorly understood. This is particularly evident in physiological and anatomical disorders that inhibit plant development and wood quality. We aimed to explore how the supply of Ca and Mg through liming (lime), combined with Cu and Zn fertilization (CZF), influences physiological and anatomical responses during Eucalyptus grandis seedlings growth in tropical acid soil. Therefore, related parameters of leaf area and leaf anatomy, stomatal size, leaf gas exchange, antioxidant system, nutrient partitioning, and biomass allocation responses were monitored. Liming alone in Eucalyptus increased specific leaf area, stomatal density on the abaxial leaf surface, and Ca and Mg content. Also, Eucalyptus exposed only to CZF increased Cu and Zn content. Lime and CZF increased leaf blade and adaxial epidermal thickness, and improved the structural organization of the spongy mesophyll, promoting increased net CO2 assimilation, and stomatal conductance. Fertilization with Ca, Mg, Cu, and Zn positively affects plant nutrition, light utilization, photosynthetic rate, and antioxidant performance, improving growth. Our results indicate that lime and CZF induce adaptive responses in the physiological and anatomical adjustments of Eucalyptus plantation, thereby promoting biomass accumulation.

Genetic drift promotes and recombination hinders speciation on holey fitness landscapes.

Dobzhansky and Muller proposed a general mechanism through which microevolution, the substitution of alleles within populations, can cause the evolution of reproductive isolation between populations and, therefore, macroevolution. As allopatric populations diverge, many combinations of alleles differing between them have not been tested by natural selection and may thus be incompatible. Such genetic incompatibilities often cause low fitness in hybrids between species. Furthermore, the number of incompatibilities grows with the genetic distance between diverging populations. However, what determines the rate and pattern of accumulation of incompatibilities remains unclear. We investigate this question by simulating evolution on holey fitness landscapes on which genetic incompatibilities can be identified unambiguously. We find that genetic incompatibilities accumulate more slowly among genetically robust populations and identify two determinants of the accumulation rate: recombination rate and population size. In large populations with abundant genetic variation, recombination selects for increased genetic robustness and, consequently, incompatibilities accumulate more slowly. In small populations, genetic drift interferes with this process and promotes the accumulation of genetic incompatibilities. Our results suggest a novel mechanism by which genetic drift promotes and recombination hinders speciation.

Cadmium tolerance in tomato: determination of organ-specific contribution by diallel analysis using reciprocal grafts.

Given the increasing problems of water and soil contamination with cadmium (Cd), it is necessary to investigate the genetic and physiological mechanisms of tolerance to this metal in different crops, which can be used for the development of effective crop management strategies. This study aimed to assess the potential of grafting as a strategy to increase Cd tolerance and reduce absorption in tomato by evaluating the contribution of the root system and aerial parts for tolerance mechanisms. To this end, reciprocal grafting and diallel analyses were used to examine the combining ability of contrasting tomato genotypes under exposure to 0 and 35 µM CdCl2. Roots and above-ground parts were found to have specific mechanisms of Cd tolerance, absorption, and accumulation. Grafting of the USP15 genotype (scion) on USP16 (rootstock) provided the greatest synergism, increasing the tolerance index and reducing the translocation index and Cd accumulation in leaves. USP163 exhibited potential for breeding programs that target genotypes with high Cd tolerance. In tomato, both Cd tolerance and accumulation in aerial parts are genotype- and tissue-specific, controlled by a complex system of complementary mechanisms that need to be better understood to support the development of strategies to reduce Cd contamination in aerial parts.

Photodynamic Therapy Directed to Melanoma Skin Cancer by Thermosensitive Hydrogel Containing Chlorophyll A.

Melanoma, a severe form of skin cancer intricately linked to genetic and environmental factors, is predicted to reach 100,000 new cases worldwide by 2040, underscoring the need for effective and safe treatment options. In this study, we assessed the efficacy of a photosensitizer called Chlorophyll A (Chl-A) incorporated into hydrogels (HGs) made of chitosan (CS) and poloxamer 407 (P407) for Photodynamic Therapy (PDT) against the murine melanoma cell line B16-F10. The HG was evaluated through various tests, including rheological studies, SEM, and ATR-FTIR, along with cell viability assays. The CS- and P407-based HGs effectively released Chl-A and possessed the necessary properties for topical application. The photodynamic activity of the HG containing Chl-A was evaluated in vitro, demonstrating high therapeutic potential, with an IC50 of 25.99 µM-an appealing result when compared to studies in the literature reporting an IC50 of 173.8 µM for cisplatin, used as a positive control drug. The developed formulation of CS and P407-based HG, serving as a thermosensitive system for topical applications, successfully controlled the release of Chl-A. In vitro cell studies associated with PDT exhibited potential against the melanoma cell line.

Mutational meltdown in asexual populations doomed to extinction.

Asexual populations are expected to accumulate deleterious mutations through a process known as Muller's ratchet. Lynch and colleagues proposed that the ratchet eventually results in a vicious cycle of mutation accumulation and population decline that drives populations to extinction. They called this phenomenon mutational meltdown. Here, we analyze mutational meltdown using a multi-type branching process model where, in the presence of mutation, populations are doomed to extinction. We analyse the change in size and composition of the population and the time of extinction under this model.

Benefits of using polymeric nanoparticles in breast cancer treatment: a systematic review.

Breast cancer comprises approximately 20% of all malignant neoplasm cases globally. Due to the limitations associated with conventional therapeutic approaches, extensive investigations have been undertaken to develop novel treatments that exhibit enhanced specificity and minimized adverse effects. Consequently, the application of polymeric nanoformulations for targeted drug delivery has gained significant attention within the biomedical field. Therefore, the primary objective of this study was to explore the inherent advantages and efficacy of employing polymeric nanoformulations for drug delivery in breast cancer treatment, as compared to traditional therapies. A comprehensive literature search was conducted across prominent databases including PubMed/MEDLINE, Embase, and Scopus, utilizing specific search strings. This meticulous approach yielded a total of 12 relevant articles for in-depth analysis and discussion. The findings from the selected studies underscore the effectiveness of employing polymeric nanoparticles as a drug delivery strategy, showcasing noteworthy improvements in cellular uptake and sustained intracellular retention of encapsulated therapeutic agents. Additionally, these nanoformulations exhibited superior efficacy, safety, and drug delivery capabilities. The utilization of polymeric nanoparticles in drug delivery has demonstrated a substantial enhancement in treatment efficacy, with the ability to achieve higher concentrations of active ingredients within tumor tissues, augment cellular uptake and drug concentrations, and sustain intracellular retention. Consequently, this innovative approach prolongs drug release in lower quantities, ultimately contributing to improved treatment outcomes.

Toxicity of bisphenol A (BPA) and its analogues BPF and BPS on the free-floating macrophyte Salvinia biloba.

Evidence linking the toxicity of bisphenol A (BPA) to environmental and public-health issues has led to restrictions on its use. This compound has been gradually replaced with analogues proposed as a safer alternative, normally bisphenol F (BPF) and bisphenol S (BPS), but these substitutes are structurally almost identical to BPA, suggesting they may pose similar risks. The effects of BPA and these analogues were compared for antioxidant activity, lipid peroxidation, free-radical generation, photosynthetic pigments, and chlorophyll fluorescence in Salvinia biloba Raddi (S. biloba) plants exposed to environmentally relevant and sublethal concentrations (1, 10, 50, 100 and 150 µM). Bisphenol exposure promoted alterations in most of the physiological parameters investigated, with BPS toxicity differing slightly from that of the analogues. Furthermore, S. biloba removed similar levels of BPA and BPF from aqueous solutions with ≈70% removed at the 150 µM concentration, while BPS was less effectively removed, with only 23% removed at 150 µM. These findings show that high concentrations of bisphenols (10≥) are toxic to S. biloba, and even typical environmental levels (≤1 µM) can induce metabolic changes in plants, bringing to light that both BPA and its substitutes BPF and BPS pose risks to aquatic ecosystems.

Mechanisms of Mucor sp. CM3 isolated from the aquatic macrophyte Eichhornia crassipes (Mart.) Solms to increase cadmium bioremediation.

Bioremediation of toxic metals is a feasible and low-cost remediation tool to reduce metal contamination. Plant-fungus interactions can improve this technique. Eichhornia crassipes (Mart.) Solms is a macrophyte reported to bioremediate contaminated water. Thus, the present study aimed to isolate endophytic fungi from E. crassipes, select a highly cadmium (Cd) tolerant isolate and evaluate its bioremediation potential. This was evaluated by (1) the fungus tolerance and capacity to accumulate Cd; (2) Cd effects on cell morphology (using SEM and TEM) and on the fungal antioxidant defense system, as well as (3) the effect on model plant Solanum lycopersicum L. cultivar Calabash Rouge, inoculated with the endophyte fungus and exposed to Cd. Our results selected the endophyte Mucor sp. CM3, which was able to tolerate up to 1000 g/L of Cd and to accumulate 900 mg of Cd/g of biomass. Significant changes in Mucor sp. CM3 morphology were observed when exposed to high Cd concentrations, retaining this metal both in its cytoplasm and in its cell wall, which may be linked to detoxification and metal sequestration mechanisms related to the formation of Cd-GSH complexes. In addition, Cd stress induced the activation of all tested antioxidant enzymes - superoxide dismutase (SOD), catalase (CAT), and glutathione reductase (GR) - in this endophytic fungus. Moreover, when inoculated in tomato plants, this fungus promoted plant growth (in treatments without Cd) and induced an increased metal translocation to plant shoot, showing its potential to increase metal bioremediation. Therefore, this study indicates that the isolated endophyte Mucor sp. CM3 can be applied as a tool in different plant conditions, improving plant bioremediation and reducing the environmental damage caused by Cd, while also promoting plant growth in the absence of contaminants.

Calcitonin as a pharmacological anchorage in orthodontics.

Objective: This study aimed to evaluate the effects of salmon calcitonin administration as a pharmacological anchoring agent in orthodontics and to determine the influence of locally applied calcitonin on serum calcium levels. The secondary aim was to observe the response of dental and periodontal tissues using light microscopy. Methods: Fourteen healthy male adult Wistar rats with an average weight of 250 g had their teeth moved, seven of which received a local injection of salmon calcitonin in the furcation region of the left upper first molar. Concurrently, the remaining seven were used as controls. In the control group, saline solution was injected in the bifurcation region of tooth 26 to subject these animals to the same stress level as those of the experimental group. After 14 days, a 6 mm diameter orthodontic elastic band was inserted between teeth 26 and 27 in all animals to induce the movement of these teeth. The rats were anaesthetised and exsanguinated on day 21. In both groups, tooth movement and serum calcium levels were measured. The jaws were dissected with straight scissors, and tissue blocks containing gingiva, bone and teeth were identified, fixed and demineralised. Then, the pieces were cut into semi-serial slices, stained with hematoxylin, eosin, and Mallory's trichrome, and analysed under an Axiophot light microscope. Results: There was significantly less tooth movement in the experimental group (X̄; 0,150 mm ± 0,037) than in the control group (0,236 mm ± 0,044; P = 0,003), while there was no significant difference in serum calcium levels between the two groups (controlX̄; 9,53 mg/dl ± 1,53; experimental 10,81 mg/dl ± 1,47; P = 0,15). Conclusion: While calcitonin did not completely inhibit osteoclast activity, it promoted orthodontic anchorage, apparently, by local action.

Grafting systems for plant cadmium research: Insights for basic plant physiology and applied mitigation.

Cadmium (Cd) is a highly toxic and carcinogenic pollutant that poses a threat to human and animal health by affecting several major organ systems. Urbanization and human activities have led to significant increases in Cd concentration in the environment, including in agroecosystems. To protect against the harmful effects of Cd, efforts are being made to promote safe crop production and to clean up Cd-contaminated agricultural lands and water, reducing Cd exposure through the consumption of contaminated agricultural products. There is a need for management strategies that can improve plant Cd tolerance and reduce Cd accumulation in crop plant tissues, all of which involve understanding the impacts of Cd on plant physiology and metabolism. Grafting, a longstanding plant propagation technique, has been shown to be a useful approach for studying the effects of Cd on plants, including insights into the signaling between organs and organ-specific modulation of plant performance under this form of environmental stress. Grafting can be applied to the large majority of abiotic and biotic stressors. In this review, we aim to highlight the current state of knowledge on the use of grafting to gain insights into Cd-induced effects as well as its potential applicability in safe crop production and phytoremediation. In particular, we emphasize the utility of heterograft systems for assessment of Cd accumulation, biochemical and molecular responses, and tolerance in crop and other plant species under Cd exposure, as well as potential intergenerational effects. We outline our perspectives and future directions for research in this area and the potential practical applicability of plant grafting, with attention to the most obvious gaps in knowledge. We aim at inspiring researchers to explore the potential of grafting for modulating Cd tolerance and accumulation and for understanding the mechanisms of Cd-induced responses in plants for both agricultural safety and phytoremediation purposes.

Ex vivo purging of cancer cells from ovarian tissue using photodynamic therapy: a novel strategy to restore fertility in leukemia patients.

STUDY QUESTION: Is it possible to purge leukemia cells from ovarian tissue (OT) fragments before transplantation? SUMMARY ANSWER: Our photodynamic therapy (PDT) approach has been shown to efficiently destroy leukemia cells from tumor-infiltration mimicking models (TIMs), indicating the feasibility of this technique to purge OT samples. WHAT IS KNOWN ALREADY: Autotransplantation of cryopreserved OT is the most suitable option to preserve fertility for prepubertal girls and women who require immediate cancer treatment. Up until now, more than 200 live births have already been reported after OT cryopreservation and transplantation. Leukemia is the 12th most common cancer in Europe among prepubertal girls and women of reproductive age and in 2020, the estimated number of new leukemia cases was higher than 33 000 in girls between 0 and 19 years old. Unfortunately, once their health has been restored, autotransplantation of cryopreserved OT for leukemia patients is not advised due to the high risk of transferring malignant cells back to the patient leading to leukemia recurrence. STUDY DESIGN SIZE DURATION: To safely transplant the OT from leukemia patients and restore their fertility, our goal was to develop a PDT strategy to eliminate leukemia ex vivo. To this end, we designed OR141-loaded niosomes (ORN) to create the most effective formulation for ex vivo purging of acute myelogenous leukemia cells from OT fragments (n = 4). Moreover, to ensure that such treatments are not harmful to follicle survival and development so they can be deemed a potential fertility restoration alternative, the effect of the ORN-based PDT purging procedure on follicles was assessed after xenografting the photodynamic-treated OT in SCID mice (n = 5). The work was carried out between September 2020 and April 2022 at the Catholic University of Louvain. PARTICIPANTS/MATERIALS SETTING METHODS: After establishing the best ORN formulation, our PDT approach was used to eradicate HL60 cells from ex vivo TIMs prepared by microinjection of a cancer cell suspension into OT fragments. The purging efficiency was analyzed by droplet digital polymerase chain reaction and immunohistochemical analyses. Additionally, we evaluated the effect of ORN-based PDT on follicle density, survival and development, and tissue quality in terms of fibrotic areas and vascularization after 7-day xenotransplantation to immunodeficient mice. MAIN RESULTS AND THE ROLE OF CHANCE: The ex vivo purging of TIMs demonstrated that our PDT strategy could selectively eradicate the malignant cells from tissue fragments without affecting OT normal cells, as evidenced by PCR and immunohistochemical analysis. Regarding the effect of our PDT approach on follicle population and OT quality, our results after xenotransplantation revealed no significant difference between the follicle density of control (non-treated, grafted OT) and PDT-treated groups (2.38 ± 0.63 and 3.21 ± 1.94 morphologically normal follicles/mm2, respectively). In addition, our findings showed that the control and PDT-treated OT could be equally vascularized (7.65 ± 1.45% and 9.89 ± 2.21%, respectively). Similarly, the proportions of fibrotic area did not differ between the control (15.96 ± 5.94%) and PDT-treated groups (13.32 ± 3.05%). LARGE SCALE DATA: N/A. LIMITATIONS REASONS FOR CAUTION: This study did not use OT fragments from leukemia patients, but TIMs created after injection of HL60 cells into OT from healthy patients. Therefore, while the results are promising, whether our PDT approach will be equally successful in eliminating malignant cells from leukemia patients remains to be assessed. WIDER IMPLICATIONS OF THE FINDINGS: Our results showed that the purging procedure causes no significant impairment effect on follicle development and tissue quality, suggesting that our novel PDT procedure could be a promising strategy to destroy leukemia cells in fragments of OT, allowing safe transplantation in cancer survivors. STUDY FUNDING/COMPETING INTERESTS: This study was supported by grants from the Fonds National de la Recherche Scientifique de Belgique (FNRS-PDR Convention grant number T.0004.20 awarded to C.A.A.); Fondation Louvain (awarded to C.A.A.; a Ph.D. scholarship awarded to S.M., as part of a legacy from Mr Frans Heyes, and a Ph.D. scholarship awarded to A.D. as part of a legacy from Mrs. Ilse Schirmer); and Foundation Against Cancer (grant number 2018-042 awarded to A.C.). The authors declare no competing interests.

Sex, amitosis, and evolvability in the ciliate Tetrahymena thermophila.

Understanding the mechanisms that generate genetic variation, and thus contribute to the process of adaptation, is a major goal of evolutionary biology. Mutation and genetic exchange have been well studied as mechanisms to generate genetic variation. However, there are additional factors, such as genome architecture, that may also impact the amount of genetic variation in some populations, and the extent to which these variation generating mechanisms are themselves shaped by natural selection is still an open question. To test the effect of genome architecture on the generation of genetic variation, and hence evolvability, we studied Tetrahymena thermophila, a ciliate with an unusual genome structure and mechanism of nuclear division, called amitosis, whereby homologous chromosomes are randomly distributed to daughter cells. Amitosis leads to genetic variation among the asexual descendants of a newly produced sexual progeny because different progeny cells will contain different combinations of parental alleles. We hypothesize that amitosis thus increases the evolvability of newly produced sexual progeny relative to their unmated parents and species that undergo mitosis. To test this hypothesis, we used experimental evolution and simulations to compare the rate of adaptation in T. thermophila populations founded by a single sexual progeny to parental populations that had not had sex in many generations. The populations founded by a sexual progeny adapted more quickly than parental populations in both laboratory populations and simulated populations. This suggests that the additional genetic variation generated by amitosis of a heterozygote can increase the rate of adaptation following sex and may help explain the evolutionary success of the unusual genetic architecture of Tetrahymena and ciliates more generally.

Neutral-to-positive cadmium effects on germination and seedling vigor, with and without seed priming.

This review gathered and analyzed data about (i) the Cd-induced impacts on seed germination and seedling vigor, and (ii) the use of different priming agents to mitigate Cd-induced impacts on the early plant development. Critical evaluation of the obtained data revealed intriguing results. First, seeds of diverse species can endure exposures to Cd. Such endurance is exhibited as maintenance of or even improvement in the seed germination and vigor (up to 15% and 70%, respectively). Second, the main factors influencing seed tolerance to Cd toxicity are related to temporal variations in anatomical, physiological, and/or biochemical features. Third, Cd can trigger diverse transgenerational effects on plants by shaping seed endophytes, by modulating seed provisioning with resources and regulatory elements, and/or by altering seed (epi)genomics. Fourth, different chemical, biological and physical priming agents can mitigate Cd-induced impacts on seeds, sometimes enhancing their performance over the control (reference) values. Overall, this review shows that the impacts of Cd on seed germination and vigor encompass not only negative outcomes but also neutral and positive ones, depending upon the Cd dose, media properties, plant species and genotypes, plant developmental stage and organ, and management approaches. Increasing our understanding of plant tolerance mechanisms against the growing background Cd pollution is relevant to support breeding programs, agricultural practices, and health-environmental policies.

New insights into cadmium tolerance and accumulation in tomato: Dissecting root and shoot responses using cross-genotype grafting.

Cadmium (Cd) is one of the most threatening soil and water contaminants in agricultural settings. In previous studies, we observed that Cd affects the metabolism and physiology of tomato (Solanum lycopersicum) plants even after short-term exposure. The objective of this research was to use cross-genotype grafting to distinguish between root- and shoot-mediated responses of tomato genotypes with contrasting Cd tolerance at the early stages of Cd exposure. This study provides the first report of organ-specific contributions in two tomato genotypes with contrasting Cd tolerance: Solanum lycopersicum cv. Calabash Rouge and Solanum lycopersicum cv. Pusa Ruby (which have been classified and further characterized as sensitive (S) and tolerant (T) to Cd, respectively). Scion S was grafted onto rootstock S (S/S) and rootstock T (S/T), and scion T was grafted onto rootstock T (T/T) and rootstock S (T/S). A 35 µM cadmium chloride (CdCl2) treatment was used for stress induction in a hydroponic system. Both shoot and root contributions to Cd responses were observed, and they varied in a genotype- and/or organ-dependent manner for nutrient concentrations, oxidative stress parameters, antioxidant enzymes, and transporters gene expression. The findings overall provide evidence for the dominant role of the tolerant rootstock system in conferring reduced Cd uptake and accumulation. The lowest leaf Cd concentrations were observed in T/T (215.11 µg g-1 DW) and S/T (235.61 µg g-1 DW). Cadmium-induced decreases in leaf dry weight were observed only in T/S (-8.20%) and S/S (-13.89%), which also were the only graft combinations that showed decreases in chlorophyll content (-3.93% in T/S and -4.05% in S/S). Furthermore, the results show that reciprocal grafting is a fruitful approach for gaining insights into the organ-specific modulation of Cd tolerance and accumulation during the early stages of Cd exposure.

Colorimetric Detection of SARS-CoV-2 Using Plasmonic Biosensors and Smartphones.

Low-cost, instrument-free colorimetric tests were developed to detect SARS-CoV-2 using plasmonic biosensors with Au nanoparticles functionalized with polyclonal antibodies (f-AuNPs). Intense color changes were noted with the naked eye owing to plasmon coupling when f-AuNPs form clusters on the virus, with high sensitivity and a detection limit of 0.28 PFU mL-1 (PFU stands for plaque-forming units) in human saliva. Plasmon coupling was corroborated with computer simulations using the finite-difference time-domain (FDTD) method. The strategies based on preparing plasmonic biosensors with f-AuNPs are robust to permit SARS-CoV-2 detection via dynamic light scattering and UV-vis spectroscopy without interference from other viruses, such as influenza and dengue viruses. The diagnosis was made with a smartphone app after processing the images collected from the smartphone camera, measuring the concentration of SARS-CoV-2. Both image processing and machine learning algorithms were found to provide COVID-19 diagnosis with 100% accuracy for saliva samples. In subsidiary experiments, we observed that the biosensor could be used to detect the virus in river waters without pretreatment. With fast responses and requiring small sample amounts (only 20 µL), these colorimetric tests can be deployed in any location within the point-of-care diagnosis paradigm for epidemiological control.

Evaluation of Biocompatibility, Anti-Inflammatory, and Antinociceptive Activities of Pequi Oil-Based Nanoemulsions in In Vitro and In Vivo Models.

Pequi oil (Caryocar brasiliense) contains bioactive compounds capable of modulating the inflammatory process; however, its hydrophobic characteristic limits its therapeutic use. The encapsulation of pequi oil in nanoemulsions can improve its biodistribution and promote its immunomodulatory effects. Thus, the objective of the present study was to formulate pequi oil-based nanoemulsions (PeNE) to evaluate their biocompatibility, anti-inflammatory, and antinociceptive effects in in vitro (macrophages­J774.16) and in vivo (Rattus novergicus) models. PeNE were biocompatible, showed no cytotoxic and genotoxic effects and no changes in body weight, biochemistry, or histology of treated animals at all concentrations tested (90−360 µg/mL for 24 h, in vitro; 100−400 mg/kg p.o. 15 days, in vivo). It was possible to observe antinociceptive effects in a dose-dependent manner in the animals treated with PeNE, with a reduction of 27 and 40% in the doses of 100 and 400 mg/kg of PeNE, respectively (p < 0.05); however, the treatment with PeNE did not induce edema reduction in animals with carrageenan-induced edema. Thus, the promising results of this study point to the use of free and nanostructured pequi oil as a possible future approach to a preventive/therapeutic complementary treatment alongside existing conventional therapies for analgesia.

Epidemiologia da mortalidade intraoperatória de um hospital público na Bahia no período de um ano / Epidemiology of intraoperative mortality of a public hospital in Bahia in a one-year period / Epidemiología de la mortalidad intraoperatoria en un hospital público de Bahía en un período de un año

A parada cardíaca com evolução para o óbito é o pior desfecho no cenário do paciente cirúrgico. A PCR intraoperatória é definida como aquela que ocorre do momento da admissão do paciente na sala cirúrgica até o fim da anestesia para o procedimento. Nesse contexto, a anestesia tem o potencial de induzir mudanças fisiológicas que interfiram na morbimortalidade do paciente cirúrgico. Avaliar a epidemiologia da mortalidade no intraoperatório do Hospital Geral Roberto Santos (HGRS) no período de um ano elucida o perfil de atendimento cirúrgico. Este estudo é do tipo transversal, retrospectivo de revisão de prontuários. Foram estudados pacientes submetidos à cirurgia eletiva ou de urgência com morte no intraoperatório, no período de junho de 2020 a junho de 2021. Dos óbitos avaliados, houve a predominância de pacientes do sexo masculino, entre 0 e 86 anos, de cirurgia de urgência e predisposição para ASA IV, tendo maior probabilidade de mortalidade. A causa mortis predominante foi choque, seguida por infarto agudo do miocárdio. As intercorrências foram bradicardia e parada cardiorrespiratória. O perfil epidemiológico do estudo em questão é muito semelhante ao de outros estudos, com restrições. Portanto, devido ao baixo número de mortes nesse período, faz-se necessária maior investigação do perfil epidemiológico, que visa analisar, juntamente, a mortalidade do intraoperatório e a mortalidade pós-operatória de trinta dias.

Cardiac arrest with evolution to death is the worst outcome in the surgical patient scenario. Intraoperative cardiac arrest is defined as that which occurs from the time of patient admission to the operating room until the end of anesthesia for the procedure. In this context, anesthesia may induce physiological changes that interfere in the surgical patient's morbidity and mortality. Assessing the epidemiology of intraoperative mortality at the Roberto Santos General Hospital (HGRS) in a one-year period contributes to elucidate the profile of surgical care. This cross-sectional, retrospective study reviewed medical records from patients who underwent elective or emergency surgery with intraoperative death from June 2020 to June 2021. Most deaths involved male patients aged between 0 and 86 years old, who underwent emergency surgery and showed predisposition for ASA IV, with a higher probability of mortality. Predominant cause of death was shock, followed by acute myocardial infarction. Complications were bradycardia and cardiorespiratory arrest. The epidemiological profile found is similar to that of other studies, with restrictions. Due to the low number of deaths in this one-year period, further investigation of the epidemiological profile is needed to jointly analyze intraoperative mortality and 30-day postoperative mortality.

El paro cardíaco con evolución a muerte es el peor desenlace en el escenario del paciente quirúrgico. El paro cardíaco intraoperatorio se define como el que ocurre desde que el paciente ingresa al quirófano hasta el final de la anestesia para el procedimiento. En ese contexto, la anestesia tiene el potencial de inducir cambios fisiológicos que interfieren en la morbimortalidad del paciente quirúrgico. La evaluación de la epidemiología de la mortalidad intraoperatoria en el Hospital General Roberto Santos (HGRS) durante un período de un año aclara el perfil de la atención quirúrgica. Se trata de un estudio transversal, retrospectivo de revisión de historias clínicas. Se estudiaron a pacientes sometidos a cirugía electiva o de emergencia con muerte intraoperatoria en el período de junio de 2020 a junio de 2021. De las muertes evaluadas hubo predominio de pacientes del sexo masculino, con edades entre 0 y 86 años, de cirugía de emergencia y predisposición para ASA IV, con mayor probabilidad de mortalidad. La causa predominante de muerte fue el shock, seguido del infarto agudo de miocardio. Las complicaciones fueron bradicardia y paro cardiorrespiratorio. El perfil epidemiológico del estudio en cuestión fue muy similar al de otros estudios, con restricciones. Por lo tanto, debido al bajo número de muertes en este período, es necesaria una mayor investigación del perfil epidemiológico, que tiene como objetivo analizar conjuntamente la mortalidad intraoperatoria y la mortalidad posoperatoria a los 30 días.

Fóruns de accountability síncrona: a dinâmica interna das audiências públicas orçamentárias / Foros sincrónicos de accountability: la dinámica interna de las audiencias públicas presupuestarias / Synchronous accountability forums: the internal dynamics of budget public hearings

Resumo As audiências públicas orçamentárias são espaços de transparência e participação social. Esses espaços podem ser considerados fóruns de accountability síncrona, em que a prestação de contas e a responsabilização podem ocorrer no mesmo momento, o que gera preocupação para o prestador de contas quanto às possíveis formas de responsabilização. Esta pesquisa teve como objetivo analisar como ocorre a dinâmica das audiências públicas orçamentárias organizadas pelas prefeituras municipais. Foi realizada uma pesquisa qualitativa interpretativista, por meio de entrevistas semiestruturadas com gestores públicos como principal fonte de coleta. Os resultados indicam que os responsáveis pelas audiências públicas adotam estratégias para minimizar os riscos reputacionais e de responsabilização. As estratégias ocorrem em diferentes momentos: (i) na etapa de preparação, com a definição das regras de participação e o uso de filtro informacional; (ii) durante a sua realização, na forma de apresentação das informações e no direcionamento de atenção do público; e (iii) na etapa pós-audiência, por meio de baixa transparência e até manipulação de documentos. A pesquisa contribui para o entendimento das audiências como fóruns de accountability esperada, em que a expectativa do prestador de contas pode direcionar a dinâmica das audiências públicas, transformando-as em um teatro. Os resultados trazem implicações para os Tribunais de Contas e o Poder Legislativo, que poderiam exercer maior controle e fiscalização das audiências; para a sociedade, que poderia atuar de forma mais ativa e organizada; e, ainda, para a legislação em vigor, que poderia estabelecer diretrizes claras para a realização das audiências.

Resumen Las audiencias públicas presupuestarias son espacios de transparencia y participación social. Estos espacios pueden considerarse como foros de accountability sincrónicos, en los que la rendición de cuentas y la responsabilización pueden ocurrir al mismo tiempo, lo que genera preocupaciones para el rendidor de cuentas sobre las posibles formas de responsabilización. Esta investigación tuvo como objetivo analizar cómo ocurre la dinámica de las audiencias públicas de presupuesto organizadas por los municipios. Se realizó una investigación cualitativa e interpretativa, utilizando como principal fuente de recolección de datos entrevistas semiestructuradas a gestores públicos. Los resultados indican que los responsables de las audiencias públicas adoptan estrategias, minimizando los riesgos reputacionales y de responsabilización. Las estrategias ocurren en diferentes momentos: (i) en la etapa de preparación, con la definición de las reglas de participación y el uso del filtro informativo; (ii) durante su ejecución, en la forma de presentar la información y dirigir la atención del público; y, (iii) en la etapa posterior a la audiencia, a través de la baja transparencia e incluso manipulación de documentos. La investigación contribuye a la comprensión de las audiencias como foros de esperada rendición de cuentas, en los que la expectativa del rendidor de cuentas puede orientar la dinámica de las audiencias públicas, transformándolas en un teatro. Los resultados tienen implicaciones para los Tribunales de Cuentas y el Poder Legislativo, que podrían ejercer un mayor control e inspección de las audiencias; para la sociedad, que podría actuar de forma más activa y organizada; y también para la legislación vigente, que podría establecer lineamientos claros para la celebración de audiencias.

Abstract Budget public hearings are spaces for transparency and social participation. These spaces can be considered synchronous accountability forums, where the rendering of accounts and the attribution of responsibilities can co-occur, raising concerns for the responsible parties about possible accountability models. This qualitative and interpretative research analyzed the dynamics of public budget hearings organized by Brazilian municipalities using semi-structured interviews with public managers. The results indicate that those responsible for public hearings adopt strategies minimizing reputational and accountability risks at different times: (i) in the preparation stage, with the definition of participation rules and the use of an informational filter; (ii) during execution, in the form of the presentation of information and in directing the public's attention; and, (iii) in the post-hearing stage, through low transparency and document manipulation. The research contributes to understanding hearings as forums of expected accountability, in which the expectation of the authorities can direct the dynamics of public hearings, transforming them into a theater performance. The results have implications for the courts of accounts and the legislative branch, which could exercise greater control and inspection of the hearings; for society, which could act in a more active and organized way; and also for the legislation in force, which could establish clear guidelines for holding hearings.

Fabrication of Functional bioMOF-100 Prototype as Drug Delivery System for Breast Cancer Therapy.

Breast cancer is the most frequent cause of cancer death in women, representing the fifth leading cause of cancer death overall. Therefore, the growing search for the development of new treatments for breast cancer has been developed lately as well as drug delivery systems such as biocompatible metal-organic Frameworks (bio-MOFs). These may be promising and attractive for drug incorporation and release. The present study aims to develop a drug carrier system RCA (bioMOF-100 submitted to the activation process) containing incorporated curcumin (CCM), whose material surface is coated with folic acid molecules (FA) to promote the targeting of drug carrier systems to the tumor region. They were synthesized and characterized using several characterization techniques. The materials were submitted to drug encapsulation tests, whose encapsulation efficiency was 32.80% for CCM@RCA-1D. Using the 1H nuclear magnetic resonance (NMR) spectroscopy technique, it was possible to verify the appearance of signals referring to folic acid, suggesting success in the functionalization of these matrices. In vitro tests such as cell viability and type of cell death were evaluated in both series of compounds (CCM@RCA-1D, CCM@RCA-1D/FA) in breast tumor lines. The results revealed low toxicity of the materials and cell death by late apoptosis. Thus, these results indicate that the matrices studied can be promising carriers in the treatment of breast cancer.